These experiments have four broad objectives: (1) to characterize the pathway and renal mechanisms by which changes in sodium excretion and renin secretion are induced by alteration of sodium concentration in the CNS, (2) to localize and better characterize the brain sodium/osmoreceptors which are involved in the above responses, (3) to evaluate the possible physiologic action of angiotension on these receptors or related neuronal elements to cause thrist and ADH secretion, (4) to evaluate the effect of psychosocial stress on renin secretion (this last objective has been covered in the first two years of the grant). Regarding goal 1, we have established in anesthetized dogs that the gross hemodynamic changes do not account for the natriuresis induced by elevated DSF (cerebrospinal) Na concentration. The role of ADH in the response will be evaluated in conscious Brattleboro rats and in conscious water-diveretic sheep, Natriuretic hormone activity (bioassay) is being measured during the natriuretic responses, with regard to (2), push-pull perfusion of a stimulus solution in the brain, and lesion techniques are being utilized in an attempt to localize the receptors, drugs known to affect sodium transport of neurons will be injected into the brain ventricles of conscious water-loaded rats to evaluate effects on sodium excretion. The physiologic role of angiotension (3) in the causation of thrist and release of ADH is being evaluated by infusing P113 (competitive antagonist of angiotensin II) into the brain ventricles of conscious animals under circumstances in which elevated renin/angiotensin might be expected to be stimulating thrist/ADH.